In the 1930s, investigators realized that there were also microscopic pathways within the heart’s interior in addition to the coronary arteries on the heart’s surface. Although this was the first time these pathways were discovered in humans, they were already known to be functioning in reptiles. For example, the hearts of alligators and snakes rely solely on these microscopic pathways for blood supply because they have no coronary arteries.

Inspired by this information, researchers considered how new pathways might be created within the human heart to increase blood flow. In the 1950s, one procedure attempted to open a new cardiac pathway by implanting the mammary artery inside the heart. Another procedure used needles to open pathways. Unfortunately, these attempts generally failed.

In the 1970s, investigators began to successfully create new pathways in animals’ hearts through the use of lasers. The procedure was then tested on human subjects, with preliminary data showing encouraging results. Initially, researchers assumed the benefits of TMR were due to the creation of new blood channels in the heart. However, later imaging studies showed that the new channels closed quickly, sometimes within an hour after the procedure. Also, the amount of blood in the heart after TMR is not greatly increased from the amount of blood before the procedure, so the explanation could not be increased blood flow to the heart. Thus, the actual mechanism of action for TMR’s benefits remains unknown.

Nevertheless, the procedure has clearly demonstrated its ability to reduce symptoms in patients suffering from chest pain. The U.S. Food and Drug Administration (FDA) has approved TMR for cases of severe angina where other therapies have not shown benefit. Hundreds of TMR procedures have now been performed around the United States and in Europe.